We propose to map and to identify genes which cause autosomal dominant congenital cataracts (ADCC). We have mapped one such gene in an ADCC family (ADCC-1) to a region of human chromosome 22 which contains three beta-crystallin genes. Since beta-crystallins are major components of the lens, the genes which encode them are likely candidate genes for ADCC. By sequencing the coding regions and exon- intron junctions of the chromosome 22 beta-crystallin genes in ADCC-1 patients and controls, we will search for a mutation associated with the disease in this family. We have identified five additional families with ADCC. We propose to conduct linkage studies on these families to map the genes responsible for ADCC in each family. Candidate genes localized within the flanking markers identified by linkage studies will be scanned for mutations. Congenital cataracts, present at birth but not always immediately noticeable, are one of the most common major abnormalities of the eye and a frequent cause of blindness in infants. At least a third of all cases of congenital cataracts are familial and the majority of these are inherited in an autosomal dominant mode. The research proposed in this application may elucidate the mechanisms responsible for the development of congenital cataracts and hence may contribute towards more effective treatments.